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通过深度转录组分析阐明动态瘤微环境以及MRE11表达模式在肝细胞癌中的治疗含义

Ruiqiu Chen^1,2,3,4, Chaohui Xiao^2,3,4, Zizheng Wang^3,4,5

¹The First School of Clinical Medicine, Lanzhou University, No. 1, Donggangxi Rd, Chengguan District, Lanzhou, 730000, Gansu, China.

Cancer cell international

|August 21, 2025

概括

在肝细胞癌 (HCC) 中,高MRE11表达促进免疫逃避和瘤进展. MRE11是HCC诊断的潜在生物标志物,也是免疫治疗的目标.

科学领域:

癌症学
免疫学
遗传学

背景情况:

肝细胞癌 (HCC) 是一种具有动态瘤微环境 (TME) 的复杂恶性瘤.
了解HCC TME中的基因调节对于开发有效疗法至关重要.

研究的目的:

通过深度转录组分析探索HCC的动态TME.
确定关键调节基因,重点关注MRE11的免疫调节和预后意义.

主要方法:

基于总结数据的门德尔随机化 (SMR) 通过与DNA损伤修复 (DDR) 基因交叉识别了MRE11.
在92名HCC患者的样本中,转录组分析,qPCR,免疫组织化学和西部抹杀评估了MRE11表达.
单细胞RNA测序 (scRNA-seq) 和空间转录组学揭示了MRE11在初级和免疫治疗后的TME机制.
机器学习算法构建了一个HCC的预后模型.

主要成果:

在初级TME中,高MRE11表达与HCC预后不佳和免疫逃避相关.
单细胞分析显示,MRE11通过巨细胞和恶性细胞的cGAS- STING和HGF- MET途径驱动免疫逃避和瘤进展.
在免疫疗法下,MRE11促进了表皮- 介质细胞过渡 (EMT) 和TME重塑,增强了免疫抑制的巨细胞活性.

结论:

MRE11关键调节HCC免疫微环境,促进免疫逃避和瘤进展.
MRE11是HCC诊断的一个有前途的生物标志物.
在HCC中,MRE11是个性化免疫治疗的潜在治疗点.

关键词:

深度转录图谱肝细胞癌其他国家机器学习瘤微环境

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